Global microRNA profiling of metastatic conjunctival melanoma

Lauge H Mikkelsen, Mette Andersen, Simon Andreasen, Ann-Cathrine Larsen, Qihua Tan, Peter B Toft, Karin Wadt, Steffen Heegaard

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

This study aimed to investigate the microRNA (miRNA) profile in primary tumors from conjunctival melanoma with and without subsequent metastatic spread along with their coupled distant metastases to identify miRNAs likely to be involved in metastatic progression. This observational study included 13 patients with metastatic conjunctival melanoma (follow-up: 1-39 years) treated at a Danish referral center. Twenty-five patients with nonmetastatic conjunctival melanoma (follow-up: 5-17 years) were included for comparison. Global miRNA profiling was performed with the Affymetrix GeneChip 4.1 microarray. Taqman qPCR arrays were used for validation. Significant differentially expressed miRNAs were defined as having a false discovery rate of less than 0.05. Primary conjunctival melanoma with and without subsequent metastatic spread clustered separately according to miRNA expression, and 15 miRNAs were found to have significant differential expression. Six miRNAs (hsa-miR-4528, hsa-miR-1270, hsa-miR-1290, hsa-mir-548f-4, hsa-mir-4278, and hsa-miR-34a-3p) were downregulated and nine miRNAs were upregulated (hsa-mir-575, hsa-miR-527, hsa-miR-518a-5p, hsa-miR-6759-5p, hsa-miR-8078, hsa-mir-4501, hsa-mir-622, hsa-mir-4698, and hsa-mir-4654) in primary conjunctival melanoma with subsequent metastatic spread. A comparison of primary conjunctival melanoma with their pair-matched metastases identified six significant differentially expressed miRNAs (hsa-miR-1246 and hsa-miR-302d-5p, hsa-mir-6084, hsa-miR-184, hsa-mir-658, and hsa-mir-4427). qPCR confirmed downregulation of hsa-miR-184 in the distant metastases when compared with the corresponding primary tumor. Primary conjunctival melanoma with and without subsequent metastatic spread separated clearly on the miRNA level when profiled with microarray-based methods. qPCR was able to replicate expression levels of one miRNA (hsa-miR-184) that was downregulated in metastases when compared with corresponding primary tumors.
OriginalsprogEngelsk
TidsskriftMelanoma Research
Vol/bind29
Udgave nummer5
Sider (fra-til)465-473
ISSN0960-8931
DOI
StatusUdgivet - okt. 2019

Fingeraftryk

MicroRNAs
Melanoma
Down-Regulation
Neoplasms
Referral and Consultation

Citer dette

Mikkelsen, L. H., Andersen, M., Andreasen, S., Larsen, A-C., Tan, Q., Toft, P. B., ... Heegaard, S. (2019). Global microRNA profiling of metastatic conjunctival melanoma. Melanoma Research, 29(5), 465-473. https://doi.org/10.1097/CMR.0000000000000606
Mikkelsen, Lauge H ; Andersen, Mette ; Andreasen, Simon ; Larsen, Ann-Cathrine ; Tan, Qihua ; Toft, Peter B ; Wadt, Karin ; Heegaard, Steffen. / Global microRNA profiling of metastatic conjunctival melanoma. I: Melanoma Research. 2019 ; Bind 29, Nr. 5. s. 465-473.
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title = "Global microRNA profiling of metastatic conjunctival melanoma",
abstract = "This study aimed to investigate the microRNA (miRNA) profile in primary tumors from conjunctival melanoma with and without subsequent metastatic spread along with their coupled distant metastases to identify miRNAs likely to be involved in metastatic progression. This observational study included 13 patients with metastatic conjunctival melanoma (follow-up: 1-39 years) treated at a Danish referral center. Twenty-five patients with nonmetastatic conjunctival melanoma (follow-up: 5-17 years) were included for comparison. Global miRNA profiling was performed with the Affymetrix GeneChip 4.1 microarray. Taqman qPCR arrays were used for validation. Significant differentially expressed miRNAs were defined as having a false discovery rate of less than 0.05. Primary conjunctival melanoma with and without subsequent metastatic spread clustered separately according to miRNA expression, and 15 miRNAs were found to have significant differential expression. Six miRNAs (hsa-miR-4528, hsa-miR-1270, hsa-miR-1290, hsa-mir-548f-4, hsa-mir-4278, and hsa-miR-34a-3p) were downregulated and nine miRNAs were upregulated (hsa-mir-575, hsa-miR-527, hsa-miR-518a-5p, hsa-miR-6759-5p, hsa-miR-8078, hsa-mir-4501, hsa-mir-622, hsa-mir-4698, and hsa-mir-4654) in primary conjunctival melanoma with subsequent metastatic spread. A comparison of primary conjunctival melanoma with their pair-matched metastases identified six significant differentially expressed miRNAs (hsa-miR-1246 and hsa-miR-302d-5p, hsa-mir-6084, hsa-miR-184, hsa-mir-658, and hsa-mir-4427). qPCR confirmed downregulation of hsa-miR-184 in the distant metastases when compared with the corresponding primary tumor. Primary conjunctival melanoma with and without subsequent metastatic spread separated clearly on the miRNA level when profiled with microarray-based methods. qPCR was able to replicate expression levels of one miRNA (hsa-miR-184) that was downregulated in metastases when compared with corresponding primary tumors.",
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Mikkelsen, LH, Andersen, M, Andreasen, S, Larsen, A-C, Tan, Q, Toft, PB, Wadt, K & Heegaard, S 2019, 'Global microRNA profiling of metastatic conjunctival melanoma', Melanoma Research, bind 29, nr. 5, s. 465-473. https://doi.org/10.1097/CMR.0000000000000606

Global microRNA profiling of metastatic conjunctival melanoma. / Mikkelsen, Lauge H; Andersen, Mette; Andreasen, Simon; Larsen, Ann-Cathrine; Tan, Qihua; Toft, Peter B; Wadt, Karin; Heegaard, Steffen.

I: Melanoma Research, Bind 29, Nr. 5, 10.2019, s. 465-473.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Global microRNA profiling of metastatic conjunctival melanoma

AU - Mikkelsen, Lauge H

AU - Andersen, Mette

AU - Andreasen, Simon

AU - Larsen, Ann-Cathrine

AU - Tan, Qihua

AU - Toft, Peter B

AU - Wadt, Karin

AU - Heegaard, Steffen

PY - 2019/10

Y1 - 2019/10

N2 - This study aimed to investigate the microRNA (miRNA) profile in primary tumors from conjunctival melanoma with and without subsequent metastatic spread along with their coupled distant metastases to identify miRNAs likely to be involved in metastatic progression. This observational study included 13 patients with metastatic conjunctival melanoma (follow-up: 1-39 years) treated at a Danish referral center. Twenty-five patients with nonmetastatic conjunctival melanoma (follow-up: 5-17 years) were included for comparison. Global miRNA profiling was performed with the Affymetrix GeneChip 4.1 microarray. Taqman qPCR arrays were used for validation. Significant differentially expressed miRNAs were defined as having a false discovery rate of less than 0.05. Primary conjunctival melanoma with and without subsequent metastatic spread clustered separately according to miRNA expression, and 15 miRNAs were found to have significant differential expression. Six miRNAs (hsa-miR-4528, hsa-miR-1270, hsa-miR-1290, hsa-mir-548f-4, hsa-mir-4278, and hsa-miR-34a-3p) were downregulated and nine miRNAs were upregulated (hsa-mir-575, hsa-miR-527, hsa-miR-518a-5p, hsa-miR-6759-5p, hsa-miR-8078, hsa-mir-4501, hsa-mir-622, hsa-mir-4698, and hsa-mir-4654) in primary conjunctival melanoma with subsequent metastatic spread. A comparison of primary conjunctival melanoma with their pair-matched metastases identified six significant differentially expressed miRNAs (hsa-miR-1246 and hsa-miR-302d-5p, hsa-mir-6084, hsa-miR-184, hsa-mir-658, and hsa-mir-4427). qPCR confirmed downregulation of hsa-miR-184 in the distant metastases when compared with the corresponding primary tumor. Primary conjunctival melanoma with and without subsequent metastatic spread separated clearly on the miRNA level when profiled with microarray-based methods. qPCR was able to replicate expression levels of one miRNA (hsa-miR-184) that was downregulated in metastases when compared with corresponding primary tumors.

AB - This study aimed to investigate the microRNA (miRNA) profile in primary tumors from conjunctival melanoma with and without subsequent metastatic spread along with their coupled distant metastases to identify miRNAs likely to be involved in metastatic progression. This observational study included 13 patients with metastatic conjunctival melanoma (follow-up: 1-39 years) treated at a Danish referral center. Twenty-five patients with nonmetastatic conjunctival melanoma (follow-up: 5-17 years) were included for comparison. Global miRNA profiling was performed with the Affymetrix GeneChip 4.1 microarray. Taqman qPCR arrays were used for validation. Significant differentially expressed miRNAs were defined as having a false discovery rate of less than 0.05. Primary conjunctival melanoma with and without subsequent metastatic spread clustered separately according to miRNA expression, and 15 miRNAs were found to have significant differential expression. Six miRNAs (hsa-miR-4528, hsa-miR-1270, hsa-miR-1290, hsa-mir-548f-4, hsa-mir-4278, and hsa-miR-34a-3p) were downregulated and nine miRNAs were upregulated (hsa-mir-575, hsa-miR-527, hsa-miR-518a-5p, hsa-miR-6759-5p, hsa-miR-8078, hsa-mir-4501, hsa-mir-622, hsa-mir-4698, and hsa-mir-4654) in primary conjunctival melanoma with subsequent metastatic spread. A comparison of primary conjunctival melanoma with their pair-matched metastases identified six significant differentially expressed miRNAs (hsa-miR-1246 and hsa-miR-302d-5p, hsa-mir-6084, hsa-miR-184, hsa-mir-658, and hsa-mir-4427). qPCR confirmed downregulation of hsa-miR-184 in the distant metastases when compared with the corresponding primary tumor. Primary conjunctival melanoma with and without subsequent metastatic spread separated clearly on the miRNA level when profiled with microarray-based methods. qPCR was able to replicate expression levels of one miRNA (hsa-miR-184) that was downregulated in metastases when compared with corresponding primary tumors.

U2 - 10.1097/CMR.0000000000000606

DO - 10.1097/CMR.0000000000000606

M3 - Journal article

C2 - 30932942

VL - 29

SP - 465

EP - 473

JO - Melanoma Research

JF - Melanoma Research

SN - 0960-8931

IS - 5

ER -

Mikkelsen LH, Andersen M, Andreasen S, Larsen A-C, Tan Q, Toft PB et al. Global microRNA profiling of metastatic conjunctival melanoma. Melanoma Research. 2019 okt;29(5):465-473. https://doi.org/10.1097/CMR.0000000000000606